Transcriptional regulation of neural stem cell expansion in adult hippocampus

Abstract

Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands. The identities of transcription factors regulating RGL symmetric self-renewal, unlike those that regulate RGL asymmetric self-renewal, are not known. Here, we show that the transcription factor Kruppel-like factor 9 (Klf9) is elevated in quiescent RGLs and inducible, deletion of Klf9 promotes RGL activation state. Clonal analysis and longitudinal intravital 2-photon imaging directly demonstrate that Klf9 functions as a brake on RGL symmetric self-renewal. In vivo translational profiling of RGLs lacking Klf9 generated a blueprint of RGL symmetric self-renewal for stem cell community. Together, these observations identify Klf9 as a transcriptional regulator of neural stem cell expansion in the adult hippocampus.

The Conserved Transcription Factor Krüppel Regulates the Survival and Neurogenesis of Mushroom Body Neuroblasts inDrosophilaAdult Brains

“…Cyclic expression of these factors, including KLF4, in mouse NSCs inhibits aging phenotypes in long-term in vitro culture 70 . Another Kr orthologue, KLF9, is expressed in NSCs in the hippocampus of adult mice to maintain NSC quiescence, and its forced expression in mature dentate granule cells promotes the activation of adult NSCs in a non-cell-autonomous manner 71,72 . Thus, Kr family proteins play a crucial role in controlling the longevity and proliferative capacity of NSCs across invertebrate and vertebrate species.…”